Recurrent syncope driven by unique‐variant angina pectoris

Key Clinical Message The patient's vasospastic variant angina manifested as syncope with asymptomatic ischemic episodes, and repeated 24‐h dynamic electrocardiogram and coronary angiography examinations combined with coronary provocation spasm tests were necessary for its diagnosis and management.


| INTRODUCTION
Vasospastic angina (VSA) is variant form of angina pectoris that often occurs at night or at rest, with transient ST-segment elevation observed on electrocardiography (ECG) during an attack of chest pain. 1 Cardiogenic syncope is often due to severe arrhythmias (e.g., highdegree atrioventricular block, ventricular tachycardia, and ventricular fibrillation) in response to ischemic stress. 2Clinical evidence has shown that variant angina manifests as syncope with typical ischemic episodes. 3wever, some cases of night-time atypical variant angina-related cardiogenic syncope are particularly difficult to differentiate from neurogenic syncope, leading to delays in treatment.Lifestyle changes and pharmacotherapy (e.g., non-dihydropyridines calcium-channel blockers [CCBs], statins, nitrates, nicorandil, α1adrenergic receptor antagonists, rho-kinase inhibitors, etc.) have been proposed to treat patients with VSA. 4 Herein, we describe the case of a patient with midnight syncope with no-flow limiting stenosis; he was eventually observed to have paroxysmal transient ST-segment elevation with a combined Type II (2:1 downward transmission) and Type I second-degree AV block that met the diagnostic criteria for vasospastic angina-induced syncope.

| TIME LINE
The time line of the patient's symptoms and treatment is summarized in Table 1.

| CASE PRESENTATION
A 72-year-old Chinese man who experienced syncope three times within 2 months was admitted to our cardiology department.His heart rate was 78 bpm and he was hypertensive (blood pressure 145/95 mmHg).The patient reported a >30year regular smoking habit (>8 tobacco cigarettes/ day).The laboratory examination revealed that there were no alterations in blood cardiac injury biomarkers with the exception of elevated low-density lipoprotein cholesterol (4.08 mmol/L; normal range 0.00-3.12mmol/L) and elevated N-terminal pronatriuretic peptide (NT-proBNP, 1455 pg/mL; normal range < 300 pg/mL).
Coronary angiography (CAG) showed that with the exception of the left main coronary artery, the walls of the left anterior descending and left circumflex arteries were diffuse irregularities (Figure 2A), and the middle segment of the right coronary artery (RCA) showed <50% stenosis (Figure 2B).Color Doppler ultrasound of the carotid and vertebral arteries demonstrated that the intima-media thickness of the bilateral carotid artery was thickened with multiple plaques.
A non-dihydropyridine CCB, that is, diltiazem, combined with lifestyle interventions and intensive antilipid and antihypertension medication prevented cardiac ischemic and syncope episodes for 36 months.The patient's treatments are provided in Table 1.
This case presented several characteristics: (1) all of the symptoms (syncope) occurred in the period from midnight to early morning, and the patient reported no fatigue or emotional excitement.(2) The sign of angina pectoris was not chest tightness/typical pain, but a feeling of needing to defecate.(3) The patient's ECG findings were normal in the general examination, and we eventually observed a transient ST segment elevation with a combined Type II (2:1 downward transmission) and Type I second-degree AV block.(4) CAG showed only mild lesions in the RCA.(5) The patient was an elderly male smoker with hypertension and dyslipidemia, all of which are independent risk factors for a coronary artery spasm.

| DISCUSSION
In this patient's case, the cause of syncope could not be explained by the ECG and CAG results.A fourth 24-h dynamic ECG screening was thus performed.Fortunately, the ambulatory ECG caught the patient's syncope attack showing sinus rhythm, atrial premature beat (101 times), short atrial tachycardia (one time), and ST-segment elevated 0.1-0.2mV in the II, III, and avF leads along with a combined Type II (2:1 downward transmission) and Type I seconddegree atrioventricular (AV) block (Figure 3).These findings suggested that a right coronary spasm may have caused the inferior wall myocardium, AV node ischemia, and severe arrhythmias including the Type II second-degree AV block, leading to the patient's syncope. 5ariant angina refers to a segmental or diffuse reversible spasmodic contraction of coronary artery smooth muscle in the epicardium, which leads to chest tightness, chest pain, arrhythmia, and syncope. 6,7In our patient's case, the sign of angina pectoris was not chest tightness/ typical pain, but a feeling of needing to defecate.It is rarely seen in cases of variant angina pectoris with syncope as the main manifestation in clinical practice. 4The fourth 24-h dynamic ECG caught the syncope attack and showed a combined Type II (2:1 downward transmission) and Type I second-degree AV block, and the leads of the ST segment elevation were II, III, and avF (Figure 3), which are lower-wall leads of the RCA blood-supplying territory, which is consistent with the CAG finding of mild stenosis in the RCA (Figure 2B).Because 93% of the blood supply of the AV node originates from the RCA, 8 an RCA spasm appears to have reduced or blocked the blood supply of the AV node in our patient, 5 leading to the emergence of arrhythmia, including the second-degree II AV block and/or an even higher-degree AV block.In addition, this case of variant angina occurred during the hours from midnight to early morning. 9It was reported that during this time of day, the tension of the vagus nerve is increased and vagal excitation affects the conduction system of the heart, aggravating the conduction block. 8We thus speculate that our patient's variant angina pectoris manifested mainly as syncope because of the high-degree AV block caused by a coronary spasm and increased vagal tone.This concept was further supported by our observation that the treatment of the patient with sustained-release tablets of the non-dihydropyridines CCB diltiazem-which dilates epicardial and subendocardial coronary arteries and slows down the conduction of the sinoatrial node and atrioventricular node-prevented variant angina and syncope.Moreover, the patient's follow-up data at 3, 6, 12, 24, and 36 months showed no cardiac ischemic or syncope episodes (Table 1).
Study limitations should be considered.Our patient's case highlights the limitations of routine ECG and CAG for the diagnosis of variant angina pectoris with syncope.It is well known that coronary artery spasm provocation T A B L E 1 (Continued) The part of the initial 24-h dynamic ECG at the time of the patient's presentation without syncope attack.The ECG shows only sinus rhythm and atrial premature beats (101 times), some of which were not downward transmissions.
tests (e.g., the acetylcholine challenge test, hyperventilation test, and ergometrine challenge test) can help diagnose variant angina pectoris. 10Further research is needed regarding atherosclerotic plaque and vascular spasm in variant angina patients with severe arrhythmia, including those with Type II second-degree and III AV block, especially regarding underlying coronary artery spasmrelated gene polymorphisms (e.g., endothelial nitric oxide synthase gene), 11 the clinical progression, and clinical implications.

| CONCLUSION
Twenty-four-hour dynamic ECG is an essential tool in the initial screening for variant angina with or without syncope.The important take-away message of this case report is that repeated 24-h dynamic ECG examinations will be necessary to rule out unique variant angina (as seen in this rare case) for patients with a high suspicion of cardiogenic syncope and multiple vasospastic factors.
In addition, treatment with the non-dihydropyridine CCB diltiazem combined with lifestyle interventions (smoking cessation and lowered salt intake) and/or intensive lipid reduction (for patients with hyperlipidemia) might be one of the best choices for the management of variant angina patients with or without hypertension.On the other hand, our patient had not only hypertension but also multiple lacunar infarctions with local softening without a fresh cerebral hemorrhage or infarction.He was thus advised to continue taking aspirin.][14][15]

F I G U R E 2 F I G U R E 3
Left coronary artery (LCA) and right coronary artery (RCA).(A) The walls of the left anterior descending and left circumflex arteries were irregular.(B) The middle segment of the RCA with stenosis (<50%).Part of the 24-h dynamic ECG obtained at the time of the patient's variant angina with syncope attack.ST-segment 0.1-0.2mV elevation in the interior leads (II, III, avF) with a combined Type II (2:1 downward transmission) and Type I second-degree atrioventricular (AV) block.
The timeline of the patient's symptoms, examinations, treatments, and follow-up.